The goal of this clinical research study is to find the highest tolerable dose of the combinations of pazopanib and either lapatinib or trastuzumab that can be given to patients with advanced cancer. The safety of the drug combinations will also be studied.

Pazopanib is designed to block the growth of blood vessels that supply nutrients needed for tumor growth. This may prevent or slow the growth of cancer cells.

Lapatinib is designed to prevent or slow down the growth of cancer cells by blocking 2 proteins on the surface of the cancer cell, which are HER 1 and HER 2 receptors.

Trastuzumab is designed to prevent or slow down the growth of cancer cells by blocking proteins inside the cancer cell, called the Her2/neu receptor.

MTD is defined as highest dose in which incidence of dose limiting toxicity (DLT) was less than 33% (approximately two or more participants in a dose cohort).

Tumor Response [ Time Frame: End of second 28 day cycle ] [ Designated as safety issue: No ]

Computed tomography (CT) scan, magnetic resonance imaging (MRI) scan, positron emission tomography (PET) scan, and/or x-ray to check the status of the disease. Tumor response calculated by Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization Working Group (WHO) criteria. A tumor response is defined as one or more of the following: (1) stable disease for more than or equal to 4 months, (2) decrease in measurable tumor (sentinel lesions) by more than or equal to 20% by RECIST criteria, (3) decrease in tumor markers by more than or equal to 25% or (4) a partial response according to the Choi criteria.

Oral Pazopanib 200 mg every other day starting on day 1 and oral Lapatinib 500 mg daily starting day 1, both for 28 days.

Drug: Pazopanib

Starting dose: 200 mg by mouth every other day starting on day 1 for 28 days.

Other Name: GW78634

Drug: Lapatinib

Starting dose 500 mg by mouth every day for 28 days.

Other Names:

Tykerb

GW572016

Experimental: Arm B: Pazopanib + Trastuzumab

Oral Pazopanib 200 mg daily for 28 day cycle and Trastuzumab (Herceptin®) 4 mg/kg loading dose as a 90 minute infusion by vein on day 1 of cycle 1, with a maintenance dose of 2 mg/kg every week as 30 minute infusion by vein.

Drug: Trastuzumab (Herceptin®)

4 mg/kg loading dose as a 90 minute infusion by vein on day 1 of cycle 1.

A woman is eligible to enter and participate in the study if she is of non-childbearing potential (i.e., physiologically incapable of becoming pregnant), including any female who has had a hysterectomy, bilateral oophorectomy (ovariectomy), bilateral tubal ligation, is post-menopausal (total cessation of menses for ≥ 1 year); OR if of childbearing potential, has a negative serum pregnancy test at screening, and agrees to use adequate contraception.

A man with a female partner of childbearing potential is eligible to enter and participate in the study if he uses a barrier method of contraception or abstinence during the study.

Signed informed consent approved by the Institutional Review Board prior to patient entry.

History of myocardial infarction, admission for unstable angina, cardiac angioplasty or stenting within three months of Day 1 of treatment period.

History of venous or arterial thrombosis within 3 months of Day 1 of treatment Period.

Current use of therapeutic warfarin. NOTE: both low molecular weight heparin and prophylactic low-dose warfarin are permitted; however, PT/PTT must meet above inclusion criteria.

Excessive risk of bleeding or thrombosis as defined by stroke or severe bleeding within the prior 6 months.

Patients who received investigational drugs, chemotherapy or immunotherapy patient must be >/= five half-lives or >/= 3 weeks from the last dose of treatment, whichever is shorter.

Any major surgery or radiotherapy within 14 days of treatment.

Patients with a documented Left Ventricular Ejection Fraction < 45%.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01454804